Is DMD p.Thr715Ser (c.2143A>T) pathogenic?

DMD p.Thr715Ser (c.2143A>T) is classified Benign/Likely benign in DMD (ClinVar, Multiple submitters, 16 submitters; last evaluated 2026-02-04). AlphaMissense: likely benign (0.1121); Low-frequency (popmax 1.95%, afr); Associated with dilated cardiomyopathy 3B.

What condition is associated with DMD p.Thr715Ser (c.2143A>T)?

DMD p.Thr715Ser (c.2143A>T) is associated with dilated cardiomyopathy 3B, cardiomyopathy, Becker muscular dystrophy (ClinVar).

How common is DMD p.Thr715Ser (c.2143A>T) in the general population?

DMD p.Thr715Ser (c.2143A>T) is low-frequency (popmax 1.95%, afr) (gnomAD).

What do computational predictors say about DMD p.Thr715Ser (c.2143A>T)?

AlphaMissense predicts likely benign (score 0.1121) — an in-silico prediction, not a clinical call.

DMD p.Thr715Ser

c.2143A>T · rs16998350 · VCV94494

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 16 submitters

AlphaMissense

likely benign

0.1121 · ACMG-weighted

gnomAD v4.1

Rare

low-frequency (popmax 1.95%, afr)

Missense predictors

0/2 damaging

AlphaMissense, REVEL

Conditions

dilated cardiomyopathy 3B

Computational evidence

Protein change
AlphaMissense	0.1121	likely benign
REVEL	0.031	moderately benign-leaning
⇒ AlphaMissense and REVEL both call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 1.2	GERP -3.5, phastCons 0.98
Regional constraint	o/e 1.36	unconstrained · MANE · 1,863 kb · p 2.4e-62 · regional, not allelic
Overall
CADD	15.24	PHRED · no single calibrated threshold — expert panels disagree

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 1.95% African / African-American · 1,114/57,212 alleles

Filtering AF 1.85% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.81%

Overall 0.109% 1,314/1,209,230 alleles · low-frequency

Ancestry group	Frequency	1 in
African / African-Americangrpmax	1.95%	51
Remaining individualsnot grpmax-eligible	0.132%	755
Admixed American	0.127%	788
Middle Eastern	0.0231%	4,328
European (non-Finnish)	0.00872%	11,469

Rarity supports pathogenicity (ACMG PM2); frequency above a disease-specific BA1/BS1 threshold argues against it. A variant frequent in one ancestry group can be near-absent in others, so a single global figure can mislead.

Variant & gene context

Gene: DMD
Protein: p.Thr715Ser
Coding: c.2143A>T
MANE Select: NM_004006
dbSNP: rs16998350
Type: single nucleotide variant
Location: chrX:32545184 (GRCh38)
Residue 715: a UniProt-annotated variant site (in)

Full DMD gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

dilated cardiomyopathy 3B — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: cardiomyopathy Becker muscular dystrophy Duchenne muscular dystrophy

Similar variants

DMD p.Thr715Pro Uncertain significance ★★ ⚠ same residue
DMD c.10086+1G>A Pathogenic ★★ same condition
DMD c.10086+1G>T Pathogenic ★★ same condition
DMD c.10086+2T>C Pathogenic ★★ same condition
DMD c.10087-2A>G Pathogenic/Likely pathogenic ★★ same condition
DMD c.10223+1G>A Pathogenic ★★ same condition
DMD c.10223+1G>C Pathogenic ★★ same condition
DMD c.10224-2A>G Likely pathogenic ★★ same condition

Built on 18 open, versioned datasets — ClinVar, gnomAD, AlphaMissense, REVEL, ClinGen & more — plus Sugi Variant's own cross-source analysis. Source data 2026-01–2026-10, ClinVar 2026-10. Full sources & versions →

Cite Sugi Variant

Gür T. Sugi Variant: A Deterministic Per-Variant Germline Reference from a Knowledge Graph for Humans and AI Agents. 2026. doi:10.5281/zenodo.21509445. This variant: https://sugi.bio/variant/dmd-p-thr715ser (accessed [today's date]).

Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown